U.S. patent number 8,415,123 [Application Number 12/661,377] was granted by the patent office on 2013-04-09 for electromagnetic treatment apparatus and method for angiogenesis modulation of living tissues and cells.
This patent grant is currently assigned to Ivivi Health Sciences, LLC. The grantee listed for this patent is Andre' A. DiMino, Arthur A. Pilla. Invention is credited to Andre' A. DiMino, Arthur A. Pilla.
United States Patent |
8,415,123 |
Pilla , et al. |
April 9, 2013 |
Electromagnetic treatment apparatus and method for angiogenesis
modulation of living tissues and cells
Abstract
An apparatus and method for electromagnetic treatment of living
tissues and cells comprising: configuring at least one waveform
according to a mathematical model having at least one waveform
parameter, said at least one waveform to be coupled to a
angiogenesis and neovascularization target pathway structure;
choosing a value of said at least one waveform parameter so that
said at least waveform is configured to be detectable in said
angiogenesis and neovascularization target pathway structure above
background activity in said target pathway structure; generating an
electromagnetic signal from said configured at least one waveform;
and coupling said electromagnetic signal to said angiogenesis and
neovascularization target pathway structure using a coupling
device.
Inventors: |
Pilla; Arthur A. (Oakland,
NJ), DiMino; Andre' A. (Woodcliff Lake, NJ) |
Applicant: |
Name |
City |
State |
Country |
Type |
Pilla; Arthur A.
DiMino; Andre' A. |
Oakland
Woodcliff Lake |
NJ
NJ |
US
US |
|
|
Assignee: |
Ivivi Health Sciences, LLC (San
Francisco, CA)
|
Family
ID: |
35196696 |
Appl.
No.: |
12/661,377 |
Filed: |
March 15, 2010 |
Prior Publication Data
|
|
|
|
Document
Identifier |
Publication Date |
|
US 20100179373 A1 |
Jul 15, 2010 |
|
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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11110000 |
Apr 19, 2005 |
|
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60563104 |
Apr 19, 2004 |
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Current U.S.
Class: |
435/173.1;
600/14; 600/10 |
Current CPC
Class: |
C12N
13/00 (20130101); A61N 1/40 (20130101); A61N
2/02 (20130101); C12M 35/02 (20130101) |
Current International
Class: |
A61N
1/06 (20060101) |
References Cited
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Oct 1992 |
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EP |
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0500983 |
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Jul 1995 |
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EP |
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748828 |
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Apr 1933 |
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FR |
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0604107 |
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Jun 1948 |
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GB |
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Jan 1986 |
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GB |
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GB |
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JP |
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May 1983 |
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WO |
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WO |
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WO 96/11723 |
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Apr 1996 |
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WO |
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WO 2004/108208 |
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Dec 2004 |
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WO |
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|
Primary Examiner: Ketter; Jim
Attorney, Agent or Firm: Shay Glenn LLP
Parent Case Text
This application is a Divisional application of U.S.
Non-Provisional application Ser. No. 11/110,000 filed Apr. 19, 2005
hereby incorporated by reference and claims the benefit of U.S.
Provisional Application 60/563,104 filed Apr. 19, 2004 hereby
incorporated by reference.
Claims
What is claimed is:
1. A method for electromagnetic treatment of living tissues and
cells by enhancing angiogenesis and neovascularization comprising
the steps of: applying a portable electromagnetic treatment device
adjacent to a target tissue site; generating an electromagnetic
signal from at least one waveform; and coupling said
electromagnetic signal to said angiogenesis and neovascularization
target pathway structure using a coupling device; and inducing an
electromagnetic field at the target tissue site from the at least
one waveform, wherein said at least one waveform is configured to
be coupled to an angiogenesis and neovascularization target pathway
structure at the target tissue site by modulating binding of
calcium to Calmodulin, wherein the waveform induces a power that is
greater than the thermal noise power of calcium binding to
Calmodulin so that the at least one waveform is configured to be
detectable in said angiogenesis and neovascularization target
pathway structure above background activity in said angiogenesis
and neovascularization target pathway structure.
2. The method of claim 1, wherein said at least one waveform
comprises at least one of a frequency component parameter that
configures said at least one waveform to repeat between about 0.01
Hz and about 100 MHz, a burst amplitude envelope parameter that
follows a mathematically defined amplitude function, a burst width
parameter that varies at each repetition according to a
mathematically defined width function, a peak induced electric
field parameter varying between about 1 .mu.V/cm and about 100
mV/cm in said target pathway structure according to a
mathematically defined function, and a peak induced magnetic field
parameter varying between about 1 and about 0.1 T in said target
pathway structure according to a mathematically defined
function.
3. The method of claim 1, wherein said angiogenesis and
neovascularization target pathway structure includes the binding of
at least one of ions and ligands.
4. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating growth factor
production in living cells and tissues.
5. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating cytokine
production in living cells and tissues.
6. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating growth factors
and cytokines relevant to angiogenesis and neovascularization.
7. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating angiogenesis
and neovascularization for treatment of bone fractures and
disorders.
8. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating angiogenesis
and neovascularization for treatment of cardiovascular
diseases.
9. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating angiogenesis
and neovascularization for treatment of cerebral diseases.
10. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating angiogenesis
and neovascularization for treatment of cerebrovascular
disease.
11. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating angiogenesis
and neovascularization for treatment peripheral vascular
disease.
12. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating angiogenesis
and neovascularization for treatment of diseased or ischemic cells
and tissues.
13. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating angiogenesis
and neovascularization for treatment of an acute or chronic soft
tissue wound.
14. The method of claim 1, wherein said inducing an electromagnetic
field at the target tissue site comprises modulating angiogenesis
and neovascularization for treatment of sprains strains and
contusions.
15. The method of claim 1, wherein the at least one waveform
comprises frequency components for coupling to an impedance of the
binding of calcium to Calmodulin and thus the angiogenesis and
neovascularization target pathway.
16. The method of claim 15, wherein the at least one waveform
comprises frequency components that fall within the bandpass of the
kinetics of binding of calcium to Calmodulin.
17. The method of claim 1, wherein generating the electromagnetic
signal comprises generating a burst of arbitrary waveforms having a
plurality of frequency components ranging from about 0.01Hz to
about 100 MHz, the plurality of frequency components satisfying a
SNR or PSNR model for the angiogenesis and neovascularization
target pathway structure.
18. The method of claim 1, wherein the induced electromagnetic
field comprises a burst duration between about 10 msec to about 100
msec.
19. The method of claim 1, wherein the induced electromagnetic
field comprises a peak amplitude between about 1 .mu.V/cm and about
100 mV/cm.
20. The method of claim 1, wherein the at least one waveform has a
frequency of approximately 27.12 MHz.
21. The method of claim 1, wherein generating the electromagnetic
signal comprises applying a treatment regime so that the
electromagnetic signal is applied according to the treatment
regimen.
22. The method of claim 21, wherein the treatment regimen applies
the electromagnetic signal for a total time of under 1 minute to
240 minutes daily.
23. The method of claim 1, wherein the electromagnetic signal
comprises a duty cycle of between about 1 to about 10.sup.-5.
24. A method for electromagnetic treatment of living tissues and
cells by enhancing angiogenesis and neovascularization comprising
the steps of: applying a portable electromagnetic treatment device
adjacent to a target tissue site; generating an electromagnetic
signal from at least one waveform; and coupling said
electromagnetic signal to said angiogenesis and neovascularization
target pathway structure using a coupling device; and inducing an
electromagnetic field at the target tissue site from the at least
one waveform, wherein said at least one waveform is configured to
be coupled to an angiogenesis and neovascularization target pathway
structure at the target tissue site, wherein the waveform is
further configured to have a time constant that matches the
bandpass of calcium binding to Calmodulin according to an
electrically equivalent model of calcium binding to Calmodulin, and
wherein the waveform is configured to induce a power at the target
tissue that is greater than the thermal noise power of calcium
binding to Calmodulin.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention pertains generally to an apparatus and a method for
treatment of living tissues and cells by altering their interaction
with their electromagnetic environment. This invention also relates
to a method of modification of cellular and tissue growth, repair,
maintenance, and general behavior by application of encoded
electromagnetic information. More particularly this invention
relates to the application of surgically non-invasive coupling of
highly specific electromagnetic signal patterns to any number of
body parts. In particular, an embodiment according to the present
invention pertains to using pulsing electromagnetic fields ("PEMF")
to enhance living tissue growth and repair via angiogenesis and
neovascularization by affecting the precursors to growth factors
and other cytokines, such as ion/ligand binding such as calcium
binding to calmodoulin.
2. Discussion of Related Art
It is now well established that application of weak non-thermal
electromagnetic fields ("EMF") can result in physiologically
meaningful in vivo and in vitro bioeffects.
EMF has been used in applications of bone repair and bone healing.
Waveforms comprising low frequency components and low power are
currently used in orthopedic clinics. Origins of using bone repair
signals began by considering that an electrical pathway may
constitute a means through which bone can adaptively respond to EMF
signals. A linear physicochemical approach employing an
electrochemical model of a cell membrane predicted a range of EMF
waveform patterns for which bioeffects might be expected. Since a
cell membrane was a likely EMF target, it became necessary to find
a range of waveform parameters for which an induced electric field
could couple electrochemically at the cellular surface, such as
voltage-dependent kinetics. Extension of this linear model also
involved Lorentz force analysis.
A pulsed radio frequency ("PRF") signal derived from a 27.12 MHz
continuous sine wave used for deep tissue healing is known in the
prior art of diathermy. A pulsed successor of the diathermy signal
was originally reported as an electromagnetic field capable of
eliciting a non-thermal biological effect in the treatment of
infections. PRF therapeutic applications have been reported for
reduction of post-traumatic and post-operative pain and edema in
soft tissues, wound healing, burn treatment and nerve regeneration.
Application of EMF for the resolution of traumatic edema has become
increasingly used in recent years. Results to date using PRF in
animal and clinical studies suggest that edema may be measurably
reduced from such electromagnetic stimulus.
Prior art considerations of EMF dosimetry have not taken into
account dielectric properties of tissue structure as opposed to the
properties of isolated cells.
In recent years, clinical use of non-invasive PRF at radio
frequencies comprised using pulsed bursts of a 27.12 MHz sinusoidal
wave, wherein each pulse burst comprises a width of sixty-five
microseconds, having approximately 1,700 sinusoidal cycles per
burst, and various burst repetition rates. By use of a
substantially single voltage amplitude envelope with each PRF
burst, one was limiting frequency components that could couple to
relevant dielectric pathways in cells and tissue.
Time-varying electromagnetic fields, comprising rectangular
waveforms such as pulsing electromagnetic fields, and sinusoidal
waveforms such as pulsed radio frequency fields ranging from
several Hertz to an about 15 to an about 40 MHz range, are
clinically beneficial when used as an adjunctive therapy for a
variety of musculoskeletal injuries and conditions.
Beginning in the 1960's, development of modern therapeutic and
prophylactic devices was stimulated by clinical problems associated
with non-union and delayed union bone fractures. Early work showed
that an electrical pathway can be a means through which bone
adaptively responds to mechanical input. Early therapeutic devices
used implanted and semi-invasive electrodes delivering direct
current ("DC") to a fracture site. Non-invasive technologies were
subsequently developed using electrical and electromagnetic fields.
These modalities were originally created to provide a non-invasive
"no-touch" means of inducing an electrical/mechanical waveform at a
cell/tissue level. Clinical applications of these technologies in
orthopaedics have led to approved applications by regulatory bodies
worldwide for treatment of fractures such as non-unions and fresh
fractures, as well as spine fusion. Presently several EMF devices
constitute the standard armamentarium of orthopaedic clinical
practice for treatment of difficult to heal fractures. The success
rate for these devices has been very high. The database for this
indication is large enough to enable its recommended use as a safe,
non-surgical, non-invasive alternative to a first bone graft.
Additional clinical indications for these technologies have been
reported in double blind studies for treatment of avascular
necrosis, tendinitis, osteoarthritis, wound repair, blood
circulation and pain from arthritis as well as other
musculoskeletal injuries.
Cellular studies have addressed effects of weak low frequency
electromagnetic fields on both signal transduction pathways and
growth factor synthesis. It can be shown that EMF stimulates
secretion of growth factors after a short, trigger-like duration.
Ion/ligand binding processes at a cell membrane are generally
considered an initial EMF target pathway structure. The clinical
relevance to treatments for example of bone repair, is upregulation
such as modulation, of growth factor production as part of normal
molecular regulation of bone repair. Cellular level studies have
shown effects on calcium ion transport, cell proliferation, Insulin
Growth Factor ("IGF-II") release, and IGF-II receptor expression in
osteoblasts. Effects on Insulin Growth Factor-I ("IGF-I") and
IGF-II have also been demonstrated in rat fracture callus.
Stimulation of transforming growth factor beta ("TGF-.beta.")
messenger RNA ("mRNA") with PEMF in a bone induction model in a rat
has been shown. Studies have also demonstrated upregulation of
TGF-.beta. mRNA by PEMF in human osteoblast-like cell line
designated MG-63, wherein there were increases in TGF-.beta.1,
collagen, and osteocalcin synthesis. PEMF stimulated an increase in
TGF-.beta.1 in both hypertrophic and atrophic cells from human
non-union tissue. Further studies demonstrated an increase in both
TGF-.beta.1 mRNA and protein in osteoblast cultures resulting from
a direct effect of EMF on a calcium/calmodulin-dependent pathway.
Cartilage cell studies have shown similar increases in TGF-.beta.1
mRNA and protein synthesis from EMF, demonstrating a therapeutic
application to joint repair. Various studies conclude that
upregulation of growth factor production may be a common
denominator in the tissue level mechanisms underlying
electromagnetic stimulation. When using specific inhibitors, EMF
can act through a calmodulin-dependent pathway. It has been
previously reported that specific PEMF and PRF signals, as well as
weak static magnetic fields, modulate Ca.sup.2+ binding to CaM in a
cell-free enzyme preparation. Additionally, upregulation of mRNA
for BMP2 and BMP4 with PEMF in osteoblast cultures and upregulation
of TGF-.beta.1 in bone and cartilage with PEMF have been
demonstrated.
However, prior art in this field does not configure waveforms based
upon a ion/ligand binding transduction pathway. Prior art waveforms
are inefficient since prior art waveforms apply unnecessarily high
amplitude and power to living tissues and cells, require
unnecessarily long treatment time, and cannot be generated by a
portable device.
Therefore, a need exists for an apparatus and a method that more
effectively modulates angiogenesis and other biochemical processes
that regulate tissue growth and repair, shortens treatment times,
and incorporates miniaturized circuitry and light weight
applicators thus allowing the apparatus to be portable and if
desired disposable. A further need exists for an apparatus and
method that more effectively modulates angiogenesis and other
biochemical processes that regulate tissue growth and repair,
shortens treatment times, and incorporates miniaturized circuitry
and light weight applicators that can be constructed to be
implantable.
SUMMARY OF THE INVENTION
An apparatus and a method for electromagnetic treatment of living
tissues and cells by altering their interaction with their
electromagnetic environment.
According to an embodiment of the present invention, by treating a
selectable body region with a flux path comprising a succession of
EMF pulses having a minimum width characteristic of at least about
0.01 microseconds in a pulse burst envelope having between about 1
and about 100,000 pulses per burst, in which a voltage amplitude
envelope of said pulse burst is defined by a randomly varying
parameter in which instantaneous minimum amplitude thereof is not
smaller than the maximum amplitude thereof by a factor of one
ten-thousandth. The pulse burst repetition rate can vary from about
0.01 to about 10,000 Hz. A mathematically definable parameter can
also be employed to define an amplitude envelope of said pulse
bursts.
By increasing a range of frequency components transmitted to
relevant cellular pathways, access to a large range of biophysical
phenomena applicable to known healing mechanisms, including
enhanced enzyme activity and growth factor and cytokine release, is
advantageously achieved.
According to an embodiment of the present invention, by applying a
random, or other high spectral density envelope, to a pulse burst
envelope of mono- or bi-polar rectangular or sinusoidal pulses
which induce peak electric fields between 10.sup.-6 and 10 volts
per centimeter (V/cm), a more efficient and greater effect can be
achieved on biological healing processes applicable to both soft
and hard tissues in humans, animals and plants. A pulse burst
envelope of higher spectral density can advantageously and
efficiently couple to physiologically relevant dielectric pathways,
such as, cellular membrane receptors, ion binding to cellular
enzymes, and general transmembrane potential changes thereby
modulating angiogenesis and neovascularization.
By advantageously applying a high spectral density voltage envelope
as a modulating or pulse-burst defining parameter, power
requirements for such modulated pulse bursts can be significantly
lower than that of an unmodulated pulse. This is due to more
efficient matching of the frequency components to the relevant
cellular/molecular process. Accordingly, the dual advantages of
enhanced transmitting dosimetry to relevant dielectric pathways and
of decreasing power requirements are achieved.
A preferred embodiment according to the present invention utilizes
a Power Signal to Noise Ratio ("Power SNR") approach to configure
bioeffective waveforms and incorporates miniaturized circuitry and
lightweight flexible coils. This advantageously allows a device
that utilizes a Power SNR approach, miniaturized circuitry, and
lightweight flexible coils, to be completely portable and if
desired to be constructed as disposable and if further desired to
be constructed as implantable.
Specifically, broad spectral density bursts of electromagnetic
waveforms, configured to achieve maximum signal power within a
bandpass of a biological target, are selectively applied to target
pathway structures such as living organs, tissues, cells and
molecules. Waveforms are selected using a unique amplitude/power
comparison with that of thermal noise in a target pathway
structure. Signals comprise bursts of at least one of sinusoidal,
rectangular, chaotic and random wave shapes, have frequency content
in a range of about 0.01 Hz to about 100 MHz at about 1 to about
100,000 bursts per second, and have a burst repetition rate from
about 0.01 to about 1000 bursts/second. Peak signal amplitude at a
target pathway structure such as tissue, lies in a range of about 1
.mu.V/cm to about 100 mV/cm. Each signal burst envelope may be a
random function providing a means to accommodate different
electromagnetic characteristics of healing tissue. A preferred
embodiment according to the present invention comprises about 0.1
to about 100 millisecond pulse burst comprising about 1 to about
200 microsecond symmetrical or asymmetrical pulses repeating at
about 0.1 to about 100 kilohertz within the burst. The burst
envelope is a modified 1/f function and is applied at random
repetition rates between about 0.1 and about 1000 Hz. Fixed
repetition rates can also be used between about 0.1 Hz and about
1000 Hz. An induced electric field from about 0.001 mV/cm to about
100 mV/cm is generated. Another embodiment according to the present
invention comprises an about 0.01 millisecond to an about 10
millisecond burst of high frequency sinusoidal waves, such as 27.12
MHz, repeating at about 1 to about 100 bursts per second. An
induced electric field from about 0.001 mV/cm to about 100 mV/cm is
generated. Resulting waveforms can be delivered via inductive or
capacitive coupling.
It is an object of the present invention to provide modulation of
electromagnetically sensitive regulatory processes at the cell
membrane and at junctional interfaces between cells.
It is another object of the present invention to provide an
electromagnetic method of treatment of living cells and tissues
comprising a broad-band, high spectral density electromagnetic
field.
It is a further object of the present invention to provide an
electromagnetic method of treatment of living cells and tissues
comprising amplitude modulation of a pulse burst envelope of an
electromagnetic signal that will induce coupling with a maximum
number of relevant EMF-sensitive pathways in cells or tissues.
It is another object of the present invention to provide increased
blood flow to affected tissues by modulating angiogenesis and
neovascualarization.
It is another object of the present invention to provide increased
blood flow to enhance viability, growth, and differentiation of
implanted cells, such as stem cells, tissues and organs.
It is another object of the present invention to provide increased
blood flow in cardiovascular diseases by modulating angiogenesis
and neovascualarization.
It is another object of the present invention to improve
micro-vascular blood perfusion and reduced transudation.
It is another object of the present invention to provide a
treatment of maladies of the bone and other hard tissue by
modulating angiogenesis and neovascularization.
It is a still further object of the present invention to provide a
treatment of edema and swelling of soft tissue by increased blood
flow through modulation of angiogenesis and neovascularization.
It is another object of the present invention to provide an
electromagnetic method of treatment of living cells and tissues
that can be used for repair of damaged soft tissue.
It is yet another object of the present invention to increase blood
flow to damaged tissue by modulation of vasodilation and
stimulating neovascularization.
It is a yet further object of the present invention to provide an
apparatus for modulation of angiogenesis and neovascularization
that can be operated at reduced power levels and still possess
benefits of safety, economics, portability, and reduced
electromagnetic interference.
It is an object of the present invention to configure a power
spectrum of a waveform by mathematical simulation by using signal
to noise ratio ("SNR") analysis to configure a waveform optimized
to modulate angiogensis and neovascualarization then coupling the
configured waveform using a generating device such as ultra
lightweight wire coils that are powered by a waveform configuration
device such as miniaturized electronic circuitry.
It is another object of the present invention to modulate
angiogenesis and neovascularization by evaluating Power SNR for any
target pathway structure such as molecules, cells, tissues and
organs of plants, animals and humans using any input waveform, even
if electrical equivalents are non-linear as in a Hodgkin-Huxley
membrane model.
It is another object of the present invention to provide a method
and apparatus for treating plants, animals and humans using
electromagnetic fields selected by optimizing a power spectrum of a
waveform to be applied to a biochemical target pathway structure to
enable modulation of angiogenesis and neovascularization within
molecules, cells, tissues and organs of a plant, animal, and
human.
It is another object of the present invention to significantly
lower peak amplitudes and shorter pulse duration. This can be
accomplished by matching via Power SNR, a frequency range in a
signal to frequency response and sensitivity of a target pathway
structure such as a molecule, cell, tissue, and organ, of plants,
animals and humans to enable modulation of angiogenesis and
neovascularization.
The above and yet other objects and advantages of the present
invention will become apparent from the hereinafter set forth Brief
Description of the Drawings, Detailed Description of the Invention,
and Claims appended herewith.
BRIEF DESCRIPTION OF THE DRAWINGS
Preferred embodiments of the present invention will be described
below in more detail, with reference to the accompanying
drawings:
FIG. 1 is a flow diagram of a electromagnetic treatment method for
angiogenesis modulation of living tissues and cells according to an
embodiment of the present invention;
FIG. 2 is a view of control circuitry according to a preferred
embodiment of the present invention;
FIG. 3 is a block diagram of miniaturized circuitry according to a
preferred embodiment of the present invention;
FIG. 4 depicts a waveform delivered to a angiogenesis and
neovascularization target pathway structure according to a
preferred embodiment of the present invention.
DETAILED DESCRIPTION
Induced time-varying currents from PEMF or PRF devices flow in a
target pathway structure such as a molecule, cell, tissue, and
organ, and it is these currents that are a stimulus to which cells
and tissues can react in a physiologically meaningful manner. The
electrical properties of a target pathway structure affect levels
and distributions of induced current. Molecules, cells, tissue, and
organs are all in an induced current pathway such as cells in a gap
junction contact. Ion or ligand interactions at binding sites on
macromolecules that may reside on a membrane surface are voltage
dependent processes, that is electrochemical, that can respond to
an induced electromagnetic field ("E"). Induced current arrives at
these sites via a surrounding ionic medium. The presence of cells
in a current pathway causes an induced current ("J") to decay more
rapidly with time ("J(t)"). This is due to an added electrical
impedance of cells from membrane capacitance and time constants of
binding and other voltage sensitive membrane processes such as
membrane transport.
Equivalent electrical circuit models representing various membrane
and charged interface configurations have been derived. For
example, in Calcium ("Ca.sup.2+") binding, the change in
concentration of bound Ca.sup.2+ at a binding site due to induced E
may be described in a frequency domain by an impedance expression
such as:
.function..omega.I.omega..times..times. ##EQU00001## which has the
form of a series resistance-capacitance electrical equivalent
circuit. Where .omega. is angular frequency defined as 2.pi.f,
where f is frequency, i=-11/2, Z.sub.b(.omega.) is the binding
impedance, and R.sub.ion and C.sub.ion are equivalent binding
resistance and capacitance of an ion binding pathway. The value of
the equivalent binding time constant,
.tau..sub.ion=R.sub.ionC.sub.ion, is related to a ion binding rate
constant, k.sub.b, via .tau..sub.ion=R.sub.ionC.sub.ion=1/k.sub.b.
Thus, the characteristic time constant of this pathway is
determined by ion binding kinetics.
Induced E from a PEMF or PRF signal can cause current to flow into
an ion binding pathway and affect the number of Ca.sup.2+ ions
bound per unit time. An electrical equivalent of this is a change
in voltage across the equivalent binding capacitance C.sub.ion,
which is a direct measure of the change in electrical charge stored
by C.sub.ion. Electrical charge is directly proportional to a
surface concentration of Ca.sup.2+ ions in the binding site, that
is storage of charge is equivalent to storage of ions or other
charged species on cell surfaces and junctions. Electrical
impedance measurements, as well as direct kinetic analyses of
binding rate constants, provide values for time constants necessary
for configuration of a PMF waveform to match a bandpass of target
pathway structures. This allows for a required range of frequencies
for any given induced E waveform for optimal coupling to target
impedance, such as bandpass.
Ion binding to regulatory molecules is a frequent EMF target, for
example Ca.sup.2+ binding to calmodulin ("CaM"). Use of this
pathway is based upon acceleration of wound repair, for example
bone repair, that involves modulation of growth factors released in
various stages of repair. Growth factors such as platelet derived
growth factor ("PDGF"), fibroblast growth factor ("FGF"), and
epidermal growth factor ("EGF") are all involved at an appropriate
stage of healing. Angiogenesis and neovascularization are also
integral to wound repair and can be modulated by PMF. All of these
factors are Ca/CaM-dependent.
Utilizing a Ca/CaM pathway a waveform can be configured for which
induced power is sufficiently above background thermal noise power.
Under correct physiological conditions, this waveform can have a
physiologically significant bioeffect.
Application of a Power SNR model to Ca/CaM requires knowledge of
electrical equivalents of Ca.sup.2+ binding kinetics at CaM. Within
first order binding kinetics, changes in concentration of bound
Ca.sup.2+ at CaM binding sites over time may be characterized in a
frequency domain by an equivalent binding time constant,
.tau..sub.ion=R.sub.ionC.sub.ion, where R.sub.ion and C.sub.ion are
equivalent binding resistance and capacitance of the ion binding
pathway. .tau..sub.ion is related to a ion binding rate constant,
k.sub.b, via .tau..sub.ion=R.sub.ionC.sub.ion=1/k.sub.b. Published
values for k.sub.b can then be employed in a cell array model to
evaluate SNR by comparing voltage induced by a PRF signal to
thermal fluctuations in voltage at a CaM binding site. Employing
numerical values for PMF response, such as
V.sub.max=6.5.times.10.sup.-7 sec.sup.-1, [Ca.sup.2+]=2.5 .mu.M,
K.sub.D=30 .mu.M, [Ca.sup.2+CaM]=K.sub.D([Ca.sup.2+]+[CaM]), yields
k.sub.b=665 sec.sup.-1 (.tau..sub.ion=1.5 msec). Such a value for
.tau..sub.ion can be employed in an electrical equivalent circuit
for ion binding while power SNR analysis can be performed for any
waveform structure.
According to an embodiment of the present invention a mathematical
model can be configured to assimilate that thermal noise is present
in all voltage dependent processes and represents a minimum
threshold requirement to establish adequate SNR. Power spectral
density, S.sub.n(.omega.), of thermal noise can be expressed as:
S.sub.n(.omega.)=4kT Re[Z.sub.M(x,.omega.)] where
Z.sub.M(x,.omega.) is electrical impedance of a target pathway
structure, x is a dimension of a target pathway structure and Re
denotes a real part of impedance of a target pathway structure.
Z.sub.M(x,.omega.) can be expressed as:
.function..omega..gamma..times..function..gamma..times..times.
##EQU00002##
This equation clearly shows that electrical impedance of the target
pathway structure, and contributions from extracellular fluid
resistance ("R.sub.e"), intracellular fluid resistance ("R.sub.i")
and intermembrane resistance ("R.sub.g") which are electrically
connected to a target pathway structure, all contribute to noise
filtering.
A typical approach to evaluation of SNR uses a single value of a
root mean square (RMS) noise voltage. This is calculated by taking
a square root of an integration of S.sub.n(.omega.)=4kT
Re[Z.sub.M(x,.omega.)] over all frequencies relevant to either
complete membrane response, or to bandwidth of a target pathway
structure. SNR can be expressed by a ratio:
.function..omega. ##EQU00003## where |V.sub.M(.omega.)| is maximum
amplitude of voltage at each frequency as delivered by a chosen
waveform to the target pathway structure.
An embodiment according to the present invention comprises a pulse
burst envelope having a high spectral density, so that the effect
of therapy upon the relevant dielectric pathways, such as, cellular
membrane receptors, ion binding to cellular enzymes and general
transmembrane potential changes, is enhanced. Accordingly by
increasing a number of frequency components transmitted to relevant
cellular pathways, a large range of biophysical phenomena, such as
modulating growth factor and cytokine release and ion binding at
regulatory molecules, applicable to known healing mechanisms is
accessible. According to an embodiment of the present invention
applying a random, or other high spectral density envelope, to a
pulse burst envelope of mono- or bi-polar rectangular or sinusoidal
pulses inducing peak electric fields between about 10.sup.-6 and
about 100 V/cm, produces a greater effect on biological healing
processes applicable to both soft and hard tissues.
According to yet another embodiment of the present invention by
applying a high spectral density voltage envelope as a modulating
or pulse-burst defining parameter, power requirements for such
amplitude modulated pulse bursts can be significantly lower than
that of an unmodulated pulse burst containing pulses within a
similar frequency range. This is due to a substantial reduction in
duty cycle within repetitive burst trains brought about by
imposition of an irregular, and preferably random, amplitude onto
what would otherwise be a substantially uniform pulse burst
envelope. Accordingly, the dual advantages, of enhanced transmitted
dosimetry to the relevant dielectric pathways and of decreased
power requirement are achieved.
Referring to FIG. 1, wherein FIG. 1 is a flow diagram of a method
for delivering electromagnetic signals to angiogenesis and
neovascularization target pathway structures such as ions and
ligands of plants, animals, and humans for therapeutic and
prophylactic purposes according to an embodiment of the present
invention. A mathematical model having at least one waveform
parameter is applied to configure at least one waveform to be
coupled to a angiogenesis and neovascularization target pathway
structure such as ions and ligands (Step 101). The configured
waveform satisfies a SNR or Power SNR model so that for a given and
known angiogenesis and neovascularization target pathway structure
it is possible to choose at least one waveform parameter so that a
waveform is detectable in the angiogenesis and neovascularization
target pathway structure above its background activity (Step 102)
such as baseline thermal fluctuations in voltage and electrical
impedance at a target pathway structure that depend upon a state of
a cell and tissue, that is whether the state is at least one of
resting, growing, replacing, and responding to injury. A preferred
embodiment of a generated electromagnetic signal is comprised of a
burst of arbitrary waveforms having at least one waveform parameter
that includes a plurality of frequency components ranging from
about 0.01 Hz to about 100 MHz wherein the plurality of frequency
components satisfies a Power SNR model (Step 102). A repetitive
electromagnetic signal can be generated for example inductively or
capacitively, from said configured at least one waveform (Step
103). The electromagnetic signal is coupled to a angiogenesis and
neovascularization target pathway structure such as ions and
ligands by output of a coupling device such as an electrode or an
inductor, placed in close proximity to the target pathway structure
(Step 104). The coupling enhances modulation of binding of ions and
ligands to regulatory molecule in living tissues and cells.
FIG. 2 illustrates a preferred embodiment of an apparatus according
to the present invention. A miniature control circuit 201 is
coupled to an end of at least one connector 202 such as wire. The
opposite end of the at least one connector is coupled to a
generating device such as a pair of electrical coils 203. The
miniature control circuit 201 is constructed in a manner that
applies a mathematical model that is used to configure waveforms.
The configured waveforms have to satisfy a SNR or Power SNR model
so that for a given and known angiogenesis and neovascularization
target pathway structure, it is possible to choose waveform
parameters that satisfy SNR or Power SNR so that a waveform is
detectable in the angiogenesis and neovascularization target
pathway structure above its background activity. A preferred
embodiment according to the present invention applies a
mathematical model to induce a time-varying magnetic field and a
time-varying electric field in a angiogenesis and
neovascularization target pathway structure such as ions and
ligands, comprising about 10 to about 100 msec bursts of about 1 to
about 100 microsecond rectangular pulses repeating at about 0.1 to
about 10 pulses per second. Peak amplitude of the induced electric
field is between about 1 uV/cm and about 100 mV/cm, varied
according to a modified 1/f function where f=frequency. A waveform
configured using a preferred embodiment according to the present
invention may be applied to a angiogenesis and neovascularization
target pathway structure such as ions and ligands for a preferred
total exposure time of under 1 minute to 240 minutes daily. However
other exposure times can be used. Waveforms configured by the
miniature control circuit 201 are directed to a generating device
203 such as electrical coils via connector 202. The generating
device 203 delivers a pulsing magnetic field configured according
to a mathematical model, that can be used to provide treatment to a
angiogenesis and neovascularization target pathway structure such
as a heart in a chest 204. The miniature control circuit applies a
pulsing magnetic field for a prescribed time and can automatically
repeat applying the pulsing magnetic field for as many applications
as are needed in a given time period, for example 10 times a day. A
preferred embodiment according to the present invention can be
positioned to treat the heart in a chest 204 by a positioning
device. Coupling a pulsing magnetic field to a angiogenesis and
neovascularization target pathway structure such as ions and
ligands, therapeutically and prophylactically reduces inflammation
thereby reducing pain and promotes healing. When electrical coils
are used as the generating device 203, the electrical coils can be
powered with a time varying magnetic field that induces a time
varying electric field in a target pathway structure according to
Faraday's law. An electromagnetic signal generated by the
generating device 203 can also be applied using electrochemical
coupling, wherein electrodes are in direct contact with skin or
another outer electrically conductive boundary of a target pathway
structure. Yet in another embodiment according to the present
invention, the electromagnetic signal generated by the generating
device 203 can also be applied using electrostatic coupling wherein
an air gap exists between a generating device 203 such as an
electrode and a angiogenesis and neovascularization target pathway
structure such as ions and ligands. An advantage of the preferred
embodiment according to the present invention is that its ultra
lightweight coils and miniaturized circuitry allow for use with
common physical therapy treatment modalities and at any body
location for which pain relief and healing is desired. An
advantageous result of application of the preferred embodiment
according to the present invention is that a living organism's
angiogenesis and neovascularization can be maintained and
enhanced.
FIG. 3 depicts a block diagram of a preferred embodiment according
to the present invention of a miniature control circuit 300. The
miniature control circuit 300 produces waveforms that drive a
generating device such as wire coils described above in FIG. 2. The
miniature control circuit can be activated by any activation means
such as an on/off switch. The miniature control circuit 300 has a
power source such as a lithium battery 301. A preferred embodiment
of the power source has an output voltage of 3.3 V but other
voltages can be used. In another embodiment according to the
present invention the power source can be an external power source
such as an electric current outlet such as an AC/DC outlet, coupled
to the present invention for example by a plug and wire. A
switching power supply 302 controls voltage to a micro-controller
303. A preferred embodiment of the micro-controller 303 uses an 8
bit 4 MHz micro-controller 303 but other bit MHz combination
micro-controllers may be used. The switching power supply 302 also
delivers current to storage capacitors 304. A preferred embodiment
of the present invention uses storage capacitors having a 220 uF
output but other outputs can be used. The storage capacitors 304
allow high frequency pulses to be delivered to a coupling device
such as inductors (Not Shown). The micro-controller 303 also
controls a pulse shaper 305 and a pulse phase timing control 306.
The pulse shaper 305 and pulse phase timing control 306 determine
pulse shape, burst width, burst envelope shape, and burst
repetition rate. An integral waveform generator, such as a sine
wave or arbitrary number generator can also be incorporated to
provide specific waveforms. A voltage level conversion sub-circuit
308 controls an induced field delivered to a target pathway
structure. A switching Hexfet 308 allows pulses of randomized
amplitude to be delivered to output 309 that routes a waveform to
at least one coupling device such as an inductor. The
micro-controller 303 can also control total exposure time of a
single treatment of a target pathway structure such as a molecule,
cell, tissue, and organ. The miniature control circuit 300 can be
constructed to apply a pulsing magnetic field for a prescribed time
and to automatically repeat applying the pulsing magnetic field for
as many applications as are needed in a given time period, for
example 10 times a day. A preferred embodiment according to the
present invention uses treatments times of about 10 minutes to
about 30 minutes.
Referring to FIG. 4 an embodiment according to the present
invention of a waveform 400 is illustrated. A pulse 401 is repeated
within a burst 402 that has a finite duration 403. The duration 403
is such that a duty cycle which can be defined as a ratio of burst
duration to signal period is between about 1 to about 10.sup.-5. A
preferred embodiment according to the present invention utilizes
pseudo rectangular 10 microsecond pulses for pulse 401 applied in a
burst 402 for about 10 to about 50 msec having a modified 1/f
amplitude envelope 404 and with a finite duration 403 corresponding
to a burst period of between about 0.1 and about 10 seconds.
EXAMPLE 1
The Power SNR approach for PMF signal configuration has been tested
experimentally on calcium dependent myosin phosphorylation in a
standard enzyme assay. The cell-free reaction mixture was chosen
for phosphorylation rate to be linear in time for several minutes,
and for sub-saturation Ca.sup.2+ concentration. This opens the
biological window for Ca.sup.2+/CaM to be EMF-sensitive. This
system is not responsive to PMF at levels utilized in this study if
Ca.sup.2+ is at saturation levels with respect to CaM, and reaction
is not slowed to a minute time range. Experiments were performed
using myosin light chain ("MLC") and myosin light chain kinase
("MLCK") isolated from turkey gizzard. A reaction mixture consisted
of a basic solution containing 40 mM Hepes buffer, pH 7.0; 0.5 mM
magnesium acetate; 1 mg/ml bovine serum albumin, 0.1% (w/v)
Tween80; and 1 mM EGTA12. Free Ca.sup.2+ was varied in the 1-7
.mu.M range. Once Ca.sup.2+ buffering was established, freshly
prepared 70 nM CaM, 160 nM MLC and 2 nM MLCK were added to the
basic solution to form a final reaction mixture. The low MLC/MLCK
ratio allowed linear time behavior in the minute time range. This
provided reproducible enzyme activities and minimized pipetting
time errors.
The reaction mixture was freshly prepared daily for each series of
experiments and was aliquoted in 100 .mu.L portions into 1.5 ml
Eppendorf tubes. All Eppendorf tubes containing reaction mixture
were kept at 0.degree. C. then transferred to a specially designed
water bath maintained at 37.+-.0.1.degree. C. by constant perfusion
of water prewarmed by passage through a Fisher Scientific model 900
heat exchanger. Temperature was monitored with a thermistor probe
such as a Cole-Parmer model 8110-20, immersed in one Eppendorf tube
during all experiments. Reaction was initiated with 2.5 .mu.M 32P
ATP, and was stopped with Laemmli Sample Buffer solution containing
30 .mu.M EDTA. A minimum of five blank samples were counted in each
experiment. Blanks comprised a total assay mixture minus one of the
active components Ca.sup.2+, CaM, MLC or MLCK. Experiments for
which blank counts were higher than 300 cpm were rejected.
Phosphorylation was allowed to proceed for 5 min and was evaluated
by counting 32P incorporated in MLC using a TM Analytic model 5303
Mark V liquid scintillation counter.
The signal comprised repetitive bursts of a high frequency
waveform. Amplitude was maintained constant at 0.2 G and repetition
rate was 1 burst/sec for all exposures. Burst duration varied from
65 .mu.sec to 1000 .mu.sec based upon projections of Power SNR
analysis which showed that optimal Power SNR would be achieved as
burst duration approached 500 .mu.sec. The results are shown in
FIG. 7 wherein burst width 701 in .mu.sec is plotted on the x-axis
and Myosin Phosphorylation 702 as treated/sham is plotted on the
y-axis. It can be seen that the PMF effect on Ca.sup.2+ binding to
CaM approaches its maximum at approximately 500 .mu.sec, just as
illustrated by the Power SNR model.
These results confirm that a PMF signal, configured according to an
embodiment of the present invention, would maximally increase
myosin phosphorylation for burst durations sufficient to achieve
optimal Power SNR for a given magnetic field amplitude.
EXAMPLE 2
According to an embodiment of the present invention use of a Power
SNR model was further verified in an in vivo wound repair model. A
rat wound model has been well characterized both biomechanically
and biochemically, and was used in this study. Healthy, young adult
male Sprague Dawley rats weighing more than 300 grams were
utilized.
The animals were anesthetized with an intraperitoneal dose of
Ketamine 75 mg/kg and Medetomidine 0.5 mg/kg. After adequate
anesthesia had been achieved, the dorsum was shaved, prepped with a
dilute betadine/alcohol solution, and draped using sterile
technique. Using a #10 scalpel, an 8-cm linear incision was
performed through the skin down to the fascia on the dorsum of each
rat. The wound edges were bluntly dissected to break any remaining
dermal fibers, leaving an open wound approximately 4 cm in
diameter. Hemostasis was obtained with applied pressure to avoid
any damage to the skin edges. The skin edges were then closed with
a 4-0 Ethilon running suture. Post-operatively, the animals
received Buprenorphine 0.1-0.5 mg/kg, intraperitoneal. They were
placed in individual cages and received food and water ad
libitum.
PMF exposure comprised two pulsed radio frequency waveforms. The
first was a standard clinical PRF signal comprising a 65 .mu.sec
burst of 27.12 MHz sinusoidal waves at 1 Gauss amplitude and
repeating at 600 bursts/sec. The second was a PRF signal
reconfigured according to an embodiment of the present invention.
For this signal burst duration was increased to 2000 .mu.sec and
the amplitude and repetition rate were reduced to 0.2 G and 5
bursts/sec respectively. PRF was applied for 30 minutes twice
daily.
Tensile strength was performed immediately after wound excision.
Two 1 cm width strips of skin were transected perpendicular to the
scar from each sample and used to measure the tensile strength in
kg/mm.sup.2. The strips were excised from the same area in each rat
to assure consistency of measurement. The strips were then mounted
on a tensiometer. The strips were loaded at 10 mm/min and the
maximum force generated before the wound pulled apart was recorded.
The final tensile strength for comparison was determined by taking
the average of the maximum load in kilograms per mm.sup.2 of the
two strips from the same wound.
The results showed average tensile strength for the 65 .mu.sec 1
Gauss PRF signal was 19.3.+-.4.3 kg/mm.sup.2 for the exposed group
versus 13.0.+-.3.5 kg/mm.sup.2 for the control group (p<0.01),
which is a 48% increase. In contrast, the average tensile strength
for the 2000 .mu.sec 0.2 Gauss PRF signal, configured according to
an embodiment of the present invention using a Power SNR model was
21.2.+-.5.6 kg/mm.sup.2 for the treated group versus 13.7.+-.4.1
kg/mm.sup.2 (p<0.01) for the control group, which is a 54%
increase. The results for the two signals were not significantly
different from each other.
These results demonstrate that an embodiment of the present
invention allowed a new PRF signal to be configured that could be
produced with significantly lower power. The PRF signal configured
according to an embodiment of the present invention, accelerated
wound repair in the rat model in a low power manner versus that for
a clinical PRF signal which accelerated wound repair but required
more than two orders of magnitude more power to produce.
EXAMPLE 3
In this example Jurkat cells react to PMF stimulation of a T-cell
receptor with cell cycle arrest and thus behave like normal
T-lymphocytes stimulated by antigens at the T-cell receptor such as
anti-CD3. For example in bone healing, results have shown both 60
Hz and PEMF fields decrease DNA synthesis of Jurkat cells, as is
expected since PMF interacts with the T-cell receptor in the
absence of a costimulatory signal. This is consistent with an
anti-inflammatory response, as has been observed in clinical
applications of PMF stimuli. The PEMF signal is more effective. A
dosimetry analysis performed according to an embodiment of the
present invention demonstrates why both signals are effective and
why PEMF signals have a greater effect than 60 Hz signals on Jurkat
cells in the most EMF-sensitive growth stage.
Comparison of dosimetry from the two signals employed involves
evaluation of the ratio of the Power spectrum of the thermal noise
voltage that is Power SNR, to that of the induced voltage at the
EMF-sensitive target pathway structure. The target pathway
structure used is ion binding at receptor sites on Jurkat cells
suspended in 2 mm of culture medium. The average peak electric
field at the binding site from a PEMF signal comprising 5 msec
burst of 200 .mu.sec pulses repeating at 15/sec, was 1 mV/cm, while
for a 60 Hz signal it was 50 .mu.V/cm.
EXAMPLE 4
In this example electromagnetic field energy was used to stimulate
neovascularization in an in vivo model. Two different signal were
employed, one configured according to prior art and a second
configured according to an embodiment of the present invention.
One hundred and eight Sprague-Dawley male rats weighing
approximately 300 grams each, were equally divided into nine
groups. All animals were anesthetized with a mixture of
ketamine/acepromazine/Stadol at 0.1 cc/g. Using sterile surgical
techniques, each animal had a 12 cm to 14 cm segment of tail artery
harvested using microsurgical technique. The artery was flushed
with 60 U/ml of heparinized saline to remove any blood or emboli.
These tail vessels, with an average diameter of 0.4 mm to 0.5 mm,
were then sutured to the transected proximal and distal segments of
the right femoral artery using two end-to-end anastomoses, creating
a femoral arterial loop. The resulting loop was then placed in a
subcutaneous pocket created over the animal's abdominal wall/groin
musculature, and the groin incision was closed with 4-0 Ethilon.
Each animal was then randomly placed into one of nine groups:
groups 1 to 3 (controls), these rats received no electromagnetic
field treatments and were killed at 4, 8, and 12 weeks; groups 4 to
6, 30 min. treatments twice a day using 0.1 gauss electromagnetic
fields for 4, 8, and 12 weeks (animals were killed at 4, 8, and 12
weeks, respectively); and groups 7 to 9, 30 min. treatments twice a
day using 2.0 gauss electromagnetic fields for 4, 8, and 12 weeks
(animals were killed at 4, 8, and 12 weeks, respectively).
Pulsed electromagnetic energy was applied to the treated groups
using a device constructed according to an embodiment of the
present invention. Animals in the experimental groups were treated
for 30 minutes twice a day at either 0.1 gauss or 2.0 gauss, using
short pulses (2 msec to 20 msec) 27.12 MHz. Animals were positioned
on top of the applicator head and confined to ensure that treatment
was properly applied. The rats were reanesthetized with
ketamine/acepromazine/Stadol intraperitoneally and 100 U/kg of
heparin intravenously. Using the previous groin incision, the
femoral artery was identified and checked for patency. The
femoral/tail artery loop was then isolated proximally and distally
from the anastomoses sites, and the vessel was clamped off. Animals
were then killed. The loop was injected with saline followed by 0.5
cc to 1.0 cc of colored latex through a 25-gauge cannula and
clamped. The overlying abdominal skin was carefully resected, and
the arterial loop was exposed. Neovascularization was quantified by
measuring the surface area covered by new blood-vessel formation
delineated by the intraluminal latex. All results were analyzed
using the SPSS statistical analysis package.
The most noticeable difference in neovascularization between
treated versus untreated rats occurred at week 4. At that time, no
new vessel formation was found among controls, however, each of the
treated groups had similar statistically significant evidence of
neovascularization at 0 cm2 versus 1.42.+-.0.80 cm2 (p<0.001).
These areas appeared as a latex blush segmentally distributed along
the sides of the arterial loop. At 8 weeks, controls began to
demonstrate neovascularization measured at 0.7.+-.0.82 cm2. Both
treated groups at 8 weeks again had approximately equal
statistically significant (p<0.001) outcroppings of blood
vessels of 3.57.+-.1.82 cm2 for the 0.1 gauss group and of
3.77.+-.1.82 cm2 for the 2.0 gauss group. At 12 weeks, animals in
the control group displayed 1.75.+-.0.95 cm2 of neovascularization,
whereas the 0.1 gauss group demonstrated 5.95.+-.3.25 cm2, and the
2.0 gauss group showed 6.20.+-.3.95 cm2 of arborizing vessels.
Again, both treated groups displayed comparable statistically
significant findings (p<0.001) over controls.
These experimental findings demonstrate that electromagnetic field
stimulation of an isolated arterial loop according to an embodiment
of the present invention increases the amount of quantifiable
neovascularization in an in vivo rat model. Increased angiogenesis
was demonstrated in each of the treated groups at each of the
sacrifice dates. No differences were found between the results of
the two gauss levels tested as predicted by the teachings of the
present invention.
Having described embodiments for an apparatus and a method for
delivering electromagnetic treatment to human, animal and plant
molecules, cells, tissue and organs, it is noted that modifications
and variations can be made by persons skilled in the art in light
of the above teachings. It is therefore to be understood that
changes may be made in the particular embodiments of the invention
disclosed which are within the scope and spirit of the invention as
defined by the appended claims.
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